Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK.
University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
Sci Rep. 2022 Jun 21;12(1):10484. doi: 10.1038/s41598-022-13825-7.
Neutrophilia and an elevated neutrophil:lymphocyte ratio are both characteristic features of severe COVID-19 infection. However, functional neutrophil responses have been poorly investigated in this setting. We utilised a novel PMA-based stimulation assay to determine neutrophil-derived reactive oxygen species (ROS) generation in patients with severe COVID-19 infection, non-COVID related sepsis and healthy study participants. ROS production was markedly elevated in COVID-19 patients with median values ninefold higher than in healthy controls and was particularly high in patients on mechanical ventilation. ROS generation correlated strongly with neutrophil count and elevated levels were also seen in patients with non-COVID related sepsis. Relative values, adjusted for neutrophil count, were high in both groups but extreme low or high values were seen in two patients who died shortly after testing, potentially indicating a predictive value for neutrophil function. Our results show that the high levels of neutrophils observed in patients with COVID-19 and sepsis exhibit functional capacity for ROS generation. This may contribute to the clinical features of acute disease and represents a potential novel target for therapeutic intervention.
中性粒细胞增多和中性粒细胞与淋巴细胞比值升高均为严重 COVID-19 感染的特征性表现。然而，在这种情况下，功能性中性粒细胞反应尚未得到充分研究。我们利用一种新型的 PMA 刺激测定法，测定了严重 COVID-19 感染、非 COVID 相关脓毒症和健康研究参与者中性粒细胞来源的活性氧 (ROS) 生成。COVID-19 患者的 ROS 产生明显升高，中位数是健康对照组的九倍，并且在接受机械通气的患者中尤其高。ROS 生成与中性粒细胞计数强烈相关，在非 COVID 相关脓毒症患者中也观察到水平升高。调整中性粒细胞计数后的相对值在两组中均较高，但在两名在检测后不久死亡的患者中，观察到极低或极高的值，这可能表明中性粒细胞功能具有预测价值。我们的结果表明，COVID-19 和脓毒症患者中观察到的高水平中性粒细胞表现出产生 ROS 的功能能力。这可能有助于急性疾病的临床特征，并代表了治疗干预的潜在新目标。
